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1.
J Biol Chem ; 300(6): 107334, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38705396

RESUMEN

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) is a critical regulator of glycolysis and plays a key role in modulating the inflammatory response, thereby contributing to the development of inflammatory diseases such as sepsis. Despite its importance, the development of strategies to target PFKFB3 in the context of sepsis remains challenging. In this study, we employed a miRNA-based approach to decrease PFKFB3 expression. Through multiple meta-analyses, we observed a downregulation of miR-106a-5p expression and an upregulation of PFKFB3 expression in clinical sepsis samples. These changes were also confirmed in blood monocytes from patients with early sepsis and from a mouse model of lipopolysaccharide (LPS)-induced sepsis. Overexpression of miR-106a-5p significantly decreased the LPS-induced increase in glycolytic capacity, inflammatory response, and pyroptosis in macrophages. Mechanistically, we identified PFKFB3 as a direct target protein of miR-106a-5p and demonstrated its essential role in LPS-induced pyroptosis and inflammatory response in macrophages. Furthermore, treatment with agomir-miR-106a-5p conferred a protective effect in an LPS mouse model of sepsis, but this effect was attenuated in myeloid-specific Pfkfb3 KO mice. These findings indicate that miR-106a-5p inhibits macrophage pyroptosis and inflammatory response in sepsis by regulating PFKFB3-mediated glucose metabolism, representing a potential therapeutic option for the treatment of sepsis.

2.
Acta Pharmacol Sin ; 45(7): 1438-1450, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38565961

RESUMEN

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.


Asunto(s)
Movimiento Celular , Dinaminas , Células Endoteliales de la Vena Umbilical Humana , Subunidad alfa del Factor 1 Inducible por Hipoxia , Ratones Endogámicos C57BL , Dinámicas Mitocondriales , Quinazolinonas , Especies Reactivas de Oxígeno , Neovascularización Retiniana , Factor A de Crecimiento Endotelial Vascular , Dinámicas Mitocondriales/efectos de los fármacos , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Dinaminas/metabolismo , Dinaminas/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismo , Quinazolinonas/farmacología , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , Neovascularización Retiniana/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Ratones , Proliferación Celular/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Angiogénesis
3.
Environ Res ; 247: 118199, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38246303

RESUMEN

Accurate detection of pollutant levels in water bodies using fusion algorithms combined with spectral data has become a critical issue for water conservation. However, the number of samples is too small and the model is unstable, which often leads to poor prediction and fails to achieve the measurement goal well. To address these challenges, this paper proposes a practical and effective method to precisely predict the concentrations of nitrite pollution in aquatic environments. The proposed method consists of three steps. Firstly, the dimension of the spectral data is reduced using Kernel Principal Component Analysis (KPCA), followed by sample augmentation using Generative Adversarial Network (GAN) to reduce calculation cost and increase the diversity and scale of the data. Secondly, several improvement strategies, including multi-cluster competitive and adaptive parameter updating, are introduced to enhance the capability of the Particle Swarm Optimization (PSO) algorithm. The improved PSO algorithm is then applied to optimize the initialization weights and biases of the Back Propagation neural network, thereby improving the model fitting and training performance. Finally, the developed prediction model is employed to predict the test set samples. The result suggests that the R2, RMSE, and MAE values are 0.976290, 0.008626, and 0.006617, which outperform the state-of-the-art and provided a promising model for the prediction of nitrite concentration in water.


Asunto(s)
Nitritos , Agua , Redes Neurales de la Computación , Algoritmos , Análisis de Componente Principal
4.
Pak J Med Sci ; 39(1): 214-218, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36694729

RESUMEN

Objectives: To investigate whether pulse index continuous cardiac output (PiCCO) and critical care ultrasound are highly consistent in volume status assessment during fluid resuscitation for septic shock patients and analyze their influence on the prognosis of septic shock. Methods: Eighty septic shock patients treated by Huizhou Central People's Hospital during December 2018 and December 2020 were included and divided into a study group and a control group by the presence of volume responsiveness, with each group having 40 patients. The control group was subject to PiCCO-guided fluid resuscitation therapy, while the study group was given fluid resuscitation therapy guided by critical care ultrasound. Cardiac output, cardiac function, and catheter-related infection (CRI) were documented for intergroup comparison to confirm whether these two techniques were consistent with each other regarding their effects on resuscitation for and prognosis of septic shock patients. Results: Mechanical ventilation duration (MVD) and intensive care unit (ICU) length of stay (LoS) were significantly shorter in the study group when compared with the control group, and the differences were statistically significant (p<0.05, respectively). In terms of blood pressure parameters, the two groups did not differ greatly in diastolic blood pressure (DBP), mean arterial pressure (MAP), systolic blood pressure (SBP), and central venous pressure (CVP) before resuscitation (p>0.05, respectively); at 6h(six hour) after resuscitation, DBP, MAP, SBP, and CVP were substantially increased in both groups as compared with the pre-resuscitation levels (all p<0.05), but the differences between the two groups lacked statistical significance (all p>0.05). Comparing urine volume and degrees of positive fluid balance at 6 h and 12 h after resuscitation, drastic increases in urine volume and positive fluid balance were observed in both groups at 12 h as compared with at 6 h (all p<0.05); nevertheless, the two groups showed no statistically significant difference in urine volume and positive fluid balance at 6 h or 12 h (p>0.05, respectively). With regards to prognosis, there was no statistically significant difference between the two groups in the number of cases of continuous renal replacement therapy (CRRT), dosage of vasoactive agents and 28-d mortality rate (all p>0.05). However, the incidence of CRI was markedly lower in the study group (0/40) as compared with the control group (5/40), and the difference was statistically significant (p<0.05). Conclusions: Both PiCCO and critical care ultrasound can help achieve favorable outcomes from resuscitation for septic shock patients. Compared with PiCCO, critical care ultrasound monitoring appears to be more effective in preventing CRI and reducing MVD and ICU LoS, thereby easing patients' medical burden.

5.
Pak J Med Sci ; 38(1): 293-296, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35035442

RESUMEN

OBJECTIVES: To investigate periodontitis risk factors and to establish a reference framework for identifying factors that place individuals at greater risk for periodontitis. METHODS: Clinical data from 80 periodontitis patients admitted in the Department of Stomatology at Hebei Provincial People's Hospital and treated between March 2020 and March 2021 were retrospectively analyzed. RESULTS: Univariate analysis showed that lower daily brushing frequencies, decreased tooth brushing duration, decreased scaling frequency, dietary habits, smoking and drinking, genetic factors, diabetes, hypertension, and obesity were more prevalent among periodontitis patients than healthy controls. Multivariate binary logistic analysis showed that daily brushing frequency, routine scaling, smoking, drinking, heredity, diabetes, hypertension, and obesity were all risk factors for periodontitis. CONCLUSIONS: There are many risk factors for periodontitis. Clinicians need to be aware of these factors for early detection and treatment of the disease.

6.
J Cell Mol Med ; 23(1): 112-125, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30353660

RESUMEN

Malignant ventricular arrhythmias (VAs) following myocardial infarction (MI) is a lethal complication resulting from sympathetic nerve hyperactivity. Numerous evidence have shown that inflammation within the paraventricular nucleus (PVN) participates in sympathetic hyperactivity. Our aim was to explore the role of Macrophage-inducible C-type lectin (Mincle) within the PVN in augmenting sympathetic activity following MI,and whether NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome/IL-1ß axis is involved in this activity. MI was induced by coronary artery ligation. Mincle expression localized in microglia within the PVN was markedly increased at 24 hours post-MI together with sympathetic hyperactivity, as indicated by measurement of the renal sympathetic nerve activity (RSNA) and norepinephrine (NE) concentration. Mincle-specific siRNA was administrated locally to the PVN, which consequently decreased microglial activation and sympathetic nerve activity. The MI rats exhibited a higher arrhythmia score after programmed electric stimulation than that treated with Mincle siRNA, suggesting that the inhibition of Mincle attenuated foetal ventricular arrhythmias post-MI. The underlying mechanism of Mincle in sympathetic hyperactivity was investigated in lipopolysaccharide (LPS)-primed naïve rats. Recombinant Sin3A-associated protein 130kD (rSAP130), an endogenous ligand for Mincle, induced high levels of NLRP3 and mature IL-1ß protein. PVN-targeted injection of NLRP3 siRNA or IL-1ß antagonist gevokizumab attenuated sympathetic hyperactivity. Together, the data indicated that the knockdown of Mincle in microglia within the PVN prevents VAs by attenuating sympathetic hyperactivity and ventricular susceptibility, in part by inhibiting its downstream NLRP3/IL-1ß axis following MI. Therapeutic interventions targeting Mincle signalling pathway could constitute a novel approach for preventing infarction injury.


Asunto(s)
Lectinas Tipo C/metabolismo , Microglía/metabolismo , Infarto del Miocardio/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Receptores Inmunológicos/metabolismo , Sistema Nervioso Simpático/metabolismo , Animales , Anticuerpos Monoclonales Humanizados/farmacología , Corazón/fisiopatología , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lectinas Tipo C/genética , Masculino , Infarto del Miocardio/genética , Infarto del Miocardio/fisiopatología , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Norepinefrina/metabolismo , Interferencia de ARN , Ratas Sprague-Dawley , Receptores Inmunológicos/genética , Sistema Nervioso Simpático/fisiopatología
7.
Sensors (Basel) ; 19(7)2019 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-30986986

RESUMEN

Tracking maneuvering targets is a challenging problem for sensors because of the unpredictability of the target's motion. Unlike classical statistical modeling of target maneuvers, a simultaneous optimization and feedback learning algorithm for maneuvering target tracking based on the Elman neural network (ENN) is proposed in this paper. In the feedback strategy, a scale factor is learnt to adaptively tune the dynamic model's error covariance matrix, and in the optimization strategy, a corrected component of the state vector is learnt to refine the final state estimation. These two strategies are integrated in an ENN-based unscented Kalman filter (UKF) model called ELM-UKF. This filter can be trained online by the filter residual, innovation and gain matrix of the UKF to simultaneously achieve maneuver feedback and an optimized estimation. Monte Carlo experiments on synthesized radar data showed that our algorithm had better performance on filtering precision compared with most maneuvering target tracking algorithms.

8.
Zhongguo Yi Liao Qi Xie Za Zhi ; 41(1): 5-8, 2017 Jan.
Artículo en Zh | MEDLINE | ID: mdl-29792643

RESUMEN

Ultrasound-based measurement of relative blood volume can be used to assess patient's dry weight during hemodialysis. The results of relative blood volume were calculated from the ultrasonic transmission time measurement in the arteriol pot, and the accuracy of transmission time measurement is directly related to the reliability of the results of relative blood volume. There are various factors which influence the travel time, this article analyzed patients themselves, measuring device and the external factors, and advised appropriate counter measures.


Asunto(s)
Volumen Sanguíneo , Diálisis Renal , Ultrasonografía , Humanos , Reproducibilidad de los Resultados
9.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(1): 254-8, 2016 Jan.
Artículo en Zh | MEDLINE | ID: mdl-27228777

RESUMEN

As the special imaging principle of the interference hyperspectral image data, there are lots of vertical interference stripes in every frames. The stripes' positions are fixed, and their pixel values are very high. Horizontal displacements also exist in the background between the frames. This special characteristics will destroy the regular structure of the original interference hyperspectral image data, which will also lead to the direct application of compressive sensing theory and traditional compression algorithms can't get the ideal effect. As the interference stripes signals and the background signals have different characteristics themselves, the orthogonal bases which can sparse represent them will also be different. According to this thought, in this paper the morphological component analysis (MCA) is adopted to separate the interference stripes signals and background signals. As the huge amount of interference hyperspectral image will lead to glow iterative convergence speed and low computational efficiency of the traditional MCA algorithm, an improved MCA algorithm is also proposed according to the characteristics of the interference hyperspectral image data, the conditions of iterative convergence is improved, the iteration will be terminated when the error of the separated image signals and the original image signals are almost unchanged. And according to the thought that the orthogonal basis can sparse represent the corresponding signals but cannot sparse represent other signals, an adaptive update mode of the threshold is also proposed in order to accelerate the computational speed of the traditional MCA algorithm, in the proposed algorithm, the projected coefficients of image signals at the different orthogonal bases are calculated and compared in order to get the minimum value and the maximum value of threshold, and the average value of them is chosen as an optimal threshold value for the adaptive update mode. The experimental results prove that whether LASIS and LAMIS image data, the traditional MCA algorithm can separate the interference stripes signals and background signals very well, and make the interference hyperspectral image decomposition perfectly, and the improved MCA algorithm not only keep the perfect results of the traditional MCA algorithm, but also can reduce the times of iteration and meet the iterative convergence conditions much faster than the traditional MCA algorithm, which will also provide a very good solution for the new theory of compressive sensing.

10.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(4): 1163-9, 2016 Apr.
Artículo en Zh | MEDLINE | ID: mdl-30052310

RESUMEN

With high-resolution spatial information and continuous spectrum information, hyperspectral remote sensing image -has a unique advantage in the field of target detection. Traditional hyperspectral remote sensing image target detection methods emphasis on using spectral information to determine deterministic algorithm and statistical algorithms. Deterministic algorithms find the target by calculating the distance between the target spectrum and detected spectrum however, they are unable to detect sub-pixel target and are easily affected by noise. Statistical methods which calculate background statistical characteristics to detect abnormal point as target. It can detect subpixel target targets and small targets better thanbig size target,. With the spatial resolution increasing, subpixel target detection target has gradually grown to a single pixel and multi-pixel target. At this point, hyperspectral image usually has large homogeneous regions where the neighboring pixels wihin the regions consist of the same type of materials and have a similar spectral characteristics, therefore, the spatial information should be needed to incorporate into the algorithm for targe detection. This paper proposes an algorithm for hyperspectral target detection combined spectrum characteristics and spatial characteristics. The algorithm is based on traditional target detection operator and combined neighborhood clustering statistics. Firstly, the algorithm uses target detection operator to divided hyperspectral image into a potential target region and background region. Then, it calculates the centroid of the potential target area. Finally, as the centroid for neighborhood clustering center to clust data in order to exclud background from potential target area, through iterative calculation to obtain the final results of the target detection. The traditional statistics algorithms defines the total image as background area in order to extract background statistics features, and the algorithm propsed devided the total image into background part and potential target part, which cut off the target interference for background statistics feature extraction. Compared with CEM operators and ACE operators, the algorithm proposed outperforms than traditional operators in big target detection .

11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(9): 2919-24, 2016 Sep.
Artículo en Zh | MEDLINE | ID: mdl-30084626

RESUMEN

Traditional hyperspectral image classification algorithms focus on spectral information application, however, with the increase of spatial resolution of hyperspectral remote sensing images, hyperspectral imaging presents clustering properties on spatial domain for the same category. It is critical for hyperspectral image classification algorithms to use spatial information in order to improve the classification accuracy. However, the marginal differences of different categories display more obviously. If it is introduced directly into the spatial-spectral sparse representation for image classification without the selection of neighborhood pixels, the classification error and the computation time will increase. This paper presents a spatial-spectral joint sparse representation classification algorithm based on neighborhood segmentation. The algorithm calculates the similarity with spectral angel in order to choose proper neighborhood pixel into spatial-spectral joint sparse representation model. With simultaneous subspace pursuit and simultaneous orthogonal matching pursuit to solve the model, the classification is determined by computing the minimum reconstruction error between testing samples and training pixels. Two typical hyperspectral images from AVIRIS and ROSIS are chosen for simulation experiment and results display that the classification accuracy of two images both improves as neighborhood segmentation threshold increasing. It concludes that neighborhood segmentation is necessary for joint sparse representation classification.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38702472

RESUMEN

RATIONALE: Methamphetamine addiction is a persistent and intractable pathological learning and memory, whereas no approved therapeutics is available. However, few attentions have been paid to how associative learning participates in the formation of intractable memory related to drug addiction OBJECTIVES AND METHODS: To investigate the role of associative learning in methamphetamine addiction and the underlying neurobiological mechanism, methamphetamine self-administration, oral sucrose self-administration, chemogenetic neuromanipulation, and fiber photometry in mice were performed in this study. RESULTS: We reported that associative learning increased methamphetamine-induced self-administration, but not oral sucrose self-administration. In addition, the enhancement of methamphetamine-induced self-administration was independent of more methamphetamine consumption, and remained with higher drug-taking and motivation in the absence of visual cues, suggesting the direct effects of the associative learning that enhanced methamphetamine-induced self-administration. Moreover, chemogenetic inactivation of the secondary visual cortex (V2) reduced the enhancement of the drug-taking induced by associative learning but did not alter sucrose-taking. Further fiber photometry of V2 neurons demonstrated that methamphetamine-associative learning elicits V2 neuron excitation, and sucrose-associative learning elicits V2 neuron inhibition. CONCLUSIONS: Therefore, this study reveals the neurobiological mechanism of V2 excitability underlying how associative learning participates in the formation of intractable memory related to drug addiction, and gives evidence to support V2 as a promising target for stimulation therapy for methamphetamine addiction.

13.
Biomed Pharmacother ; 174: 116510, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38554528

RESUMEN

BACKGROUND: CpG oligodeoxynucleotide (CpG-ODN; CpG, in short) has been employed as an adjuvant in allergen specific immunotherapy (AIT) to treat allergic diseases. The underlying mechanism needs to be further explained. The aim of this study is to examine the mechanism by which CpG and dust mite extracts (DME, a specific antigen) alleviate experimental airway allergy. METHODS: DME was used as the specific allergen to establish an airway allergy mouse model. The mice were directly exposed to DME and CpG through nasal instillations (the CpG.DME therapy). The response of DCs and allergic responses in the airways were assessed using immunological approaches. RESULTS: The airway allergy reaction was effectively suppressed by CpG.DME therapy. The administration of CpG or DME alone did not have any significant suppressive effects on the airway allergic response. Direct exposure to CpG.DME induced type 1 DCs (DC1s) and plasmacytoid DCs (pDCs), while CpG alone induced DC1s and DME alone induced DC2s in the airway tissues. Both DC1s and pDCs were required for the induction of type 1 regulatory T cells in the airway tissues by CpG.DME therapy. Depletion of either pDCs or DC1s abolished the induction of Tr1 cells, and abolished the suppressive effects on airway allergic response by the CpG.DME therapy. CONCLUSIONS: Direct exposure to CpG.DME induces DC1s and pDCs in the airway tissues. DC1s in synergy with pDCs induce type 1 regulatory T cells. The CpG.DME therapy is effective in suppressing allergic responses in mice with airway allergy.


Asunto(s)
Células Dendríticas , Ratones Endogámicos BALB C , Oligodesoxirribonucleótidos , Hipersensibilidad Respiratoria , Animales , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Oligodesoxirribonucleótidos/farmacología , Ratones , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/terapia , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Femenino , Adyuvantes Inmunológicos/farmacología , Alérgenos/inmunología , Antígenos Dermatofagoides/inmunología , Hipersensibilidad/inmunología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Pyroglyphidae/inmunología
14.
Food Chem X ; 22: 101264, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38468635

RESUMEN

Workshop with different fermentation years plays an essential role in the yield and quality of Baijiu. In actual production, the quality of base Baijiu in newly built workshop is inferior to the older one. In this study, the microbiota of workshop environment and fermentation process from two workshops namely N (ferment 2 years) and O (ferment 20 years) and flavor compounds were studied during Xiasha round. Results showed workshop O accumulated more environmental microorganisms and fungi including P. kudriavzevii, Wickerhamomyces anomalus and Saccharomyces sp mainly came from ground. Yeasts including Pichia, Cyberlindnera, Wickerhamomyces and Candida were responsible for flavor substances formation in O while Saccharopolyspora was in N. This study for the first time explored the reasons for the brewing differences among N and O workshop from perspectives of workshop environment, microbial community and flavor substances, providing new ideas for guiding production as well as improvement of Baijiu quality.

15.
Cardiovasc Res ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38626254

RESUMEN

AIM: The activation of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in endothelial cells (ECs) contributes to vascular inflammation in atherosclerosis. Considering the high glycolytic rate of ECs, we delineated whether and how glycolysis determines endothelial NLRP3 inflammasome activation in atherosclerosis. METHODS AND RESULTS: Our results demonstrated a significant upregulation of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), a key regulator of glycolysis, in human and mouse atherosclerotic endothelium, which positively correlated with NLRP3 levels. Atherosclerotic stimuli upregulated endothelial PFKFB3 expression via sterol regulatory element binding protein 2 (SREBP2) transactivation. EC-selective haplodeficiency of Pfkfb3 in Apoe-/- mice resulted in reduced endothelial NLRP3 inflammasome activation and attenuation of atherogenesis. Mechanistic investigations revealed that PFKFB3-driven glycolysis increased the NADH content and induced oligomerization of C-terminal binding protein 1 (CtBP1), an NADH-sensitive transcriptional co-repressor. The monomer form, but not the oligomer form, of CtBP1 was found to associate with the transcriptional repressor Forkhead box P1 (FOXP1) and acted as a transrepressor of inflammasome components, including NLRP3, caspase-1, and interleukin-1ß (IL-1ß). Interfering with NADH-induced CtBP1 oligomerization restored its binding to FOXP1 and inhibited the glycolysis-dependent upregulation of NLRP3, Caspase-1, and IL-1ß. Additionally, EC-specific overexpression of NADH-insensitive CtBP1 alleviates atherosclerosis. CONCLUSIONS: Our findings highlight the existence of a glycolysis-dependent NADH/CtBP/FOXP1-transrepression pathway that regulates endothelial NLRP3 inflammasome activation in atherogenesis. This pathway represents a potential target for selective PFKFB3 inhibitors or strategies aimed at disrupting CtBP1 oligomerization to modulate atherosclerosis.

16.
Int J Soc Psychiatry ; 69(8): 2018-2030, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37528555

RESUMEN

BACKGROUND: In the pandemic era, stressful life events (StressLEv) aggravated the impact on mental health. However, youths exhibited different responses to StressLEv because of diverse coping strategies, social support, and emotional intelligence before and after the pandemic. AIMS: To explore the changes in StressLEv and coping strategies before and after the coronavirus 2019 pandemic, as well as report the associations among mental health and related factors in a sample of Chinese youths experiencing the post-pandemic era. METHOD: A cross-sectional study using convenience sampling was conducted from July 1 to August 30, 2022, covering 3,038 youths aged 14 to 25 in China. Multiple logistic regression was conducted for crude odds ratios (ORs) and adjusted ORs. The relationships between lasso-selected variables was examined using structural equation modeling. RESULTS: More StressLEv and limited coping strategies were reported after the pandemic. In the post-pandemic era, BSI-positive youths (youths diagnosed as considered case by Brief Symptom Inventory, BSI) reported more StressLEv (BSI-positive: mean = 75.47; BSI-negative: mean = 28.69), less social support (BSI-positive: mean = 31.81; BSI-negative: mean = 39.22), and lower emotional intelligence (BSI-positive: mean = 75.34; BSI-negative: mean = 89.42). The willingness to engage in mental health counseling (OR: no vs. yes: 1.89; uncertain vs. yes: 4.42), being punished (OR: 1.27), adaptation problems (OR: 1.06), task-oriented coping (OR: 0.95), social diversion coping (OR: 0.90), objective support (OR: 0.90), utilization of social support (OR: 0.81), and regulation of emotion in oneself (OR: 0.94) were associated with mental health. Structural equation modeling supported our theoretical framework. CONCLUSIONS: Pandemic-induced mental health problems should not be ignored. The proposed response mechanisms could guide the development of effective interventions, which can help youths better cope with StressLEv and maintain good mental health.


Asunto(s)
Infecciones por Coronavirus , Coronavirus , Humanos , Adolescente , Salud Mental , Estudios Transversales , Pandemias , Adaptación Psicológica
17.
Hypertension ; 80(12): 2627-2640, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37795602

RESUMEN

BACKGROUND: Endothelial dysfunction plays a crucial role in aortic remodeling. Aerobic glycolysis and endothelial-to-mesenchymal transition (EndoMT) have, respectively, been suggested to contribute to endothelial dysfunction in many cardiovascular diseases. Here, we tested the hypothesis that glycolytic reprogramming is critical for EndoMT induction in aortic remodeling through an epigenetic mechanism mediated by a transcriptional corepressor CtBP1 (C-terminal binding protein 1), a sensor of glycolysis-derived NADH. METHODS: EndoMT program, aortic remodeling, and endothelial expression of the glycolytic activator PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3) were evaluated in Ang (angiotensin) II-infused mice. Mice with endothelial-specific Pfkfb3 deficiency or CtBP1 inactivation, immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter assay were employed to elucidate whether and how PFKFB3/CtBP1 epigenetically controls EndoMT. RESULTS: The EndoMT program and increased endothelial PFKFB3 expression were induced in remodeled thoracic aortas. In TGF-ß (transforming growth factor-ß)-treated human endothelial cells, activated SMAD2/3 (SMAD Family Member 2/3) transcriptionally upregulated PFKFB3 expression. In turn, the TGF-ß/SMAD signaling and EndoMT were compromised by silencing or inhibition of PFKFB3. Mechanistic studies revealed that PFKFB3-mediated glycolysis increased NADH content and activated the NADH-sensitive CtBP1. Through interaction with the transcription repressor E2F4 (E2F Transcription Factor 4), CtBP1 enhanced E2F4-mediated transcriptional repression of SMURF2 (SMAD ubiquitin regulatory factor 2), a negative regulator of TGF-ß/SMAD2 signaling. Additionally, EC-specific Pfkfb3 deficiency or CtBP1 inactivation in mice led to attenuated Ang II-induced aortic remodeling. CONCLUSIONS: Our results demonstrate a glycolysis-mediated positive feedback loop of the TGF-ß signaling to induce EndoMT and indicate that therapeutically targeting endothelial PFKFB3 or CtBP1 activity could provide a basis for treating EndoMT-linked aortic remodeling.


Asunto(s)
Angiotensina II , Células Endoteliales , Ratones , Humanos , Animales , Células Endoteliales/metabolismo , Angiotensina II/farmacología , Angiotensina II/metabolismo , NAD/metabolismo , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Factor de Crecimiento Transformador beta/metabolismo , Glucólisis , Aorta/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo
18.
Appl Biochem Biotechnol ; 194(9): 1-16, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35522362

RESUMEN

Circular RNAs (circRNAs) exert an essential function in the tumorigenesis and progression of esophageal squamous cancer (ESCC). Nonetheless, the role and potential mechanism of circ_0023984 in ESCC are blurred. circRNA expression profile data from Gene Expression Omnibus (GEO) database was applied to analyze circRNAs that were differentially expressed between ESCC tissues and paracancerous tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze circ_0023984 expression and miR-1294 expression in ESCC tissues and cells. Then a series of functional experiments were executed to validate the role of circ_0023984 and miR-1294 in modulating the proliferation, migration, invasion, and cell cycle progression of ESCC cells. Luciferase reporter experiment was performed to confirm the targeting relationship between circ_0023984 and miR-1294. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out with DAVID database. Western blot assay was utilized to detect phosphorylated-Akt (p-Akt) expression and c-Myc expression. circ_0023984 was remarkably upmodulated in ESCC tumor tissues and cell lines. circ_0023984 overexpression was correlated with advanced clinical stage and lymph node metastasis of ESCC patients. circ_0023984 overexpression remarkably enhanced ESCC cell proliferation, migration, invasion, and cell cycle progression, while knockdown of circ_0023984 showed the opposite effect. circ_0023984 was the molecular sponge of miR-1294. miR-1294 could significantly inhibit ESCC cell proliferation, migration, invasion, and induce cell cycle arrest at G0/G1 phase. circ_0023984 affected ESCC progression through regulating miR-1294 expression. The target genes of miR-1294 were associated with cell cycle arrest and PI3K-Akt signaling pathway. circ_0023984 upregulated the expression of p-Akt and c-Myc by repressing miR-1294. circ_0023984 facilitates the malignant biological behaviors of ESCC cells through inhibiting miR-1294 and activating PI3K/Akt/c-myc pathway.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-myc , ARN Circular/genética
19.
Front Oncol ; 12: 829693, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35311126

RESUMEN

Background: Recent data on first-line treatment patterns administered to hormone receptor-positive (HR+) advanced breast cancer (ABC) patients in the real-world setting are limited. This study aimed to report the first-line treatment patterns and outcomes of HR+ ABC patients in China. Methods: This was a multicenter, noninterventional study. Eligible patients were cytologically or histologically confirmed to have HR+ ABC with ≥2 complete medical records and received first-line therapies between January 2015 and June 2019. Treatment patterns and outcomes were extracted from structured or unstructured electronic medical records. Progression-free survival (PFS) was analyzed with the Kaplan-Meier method. Results: In total, 1072 patients with HR+ ABC were enrolled at 6 treatment sites: 327 human epidermal growth factor receptor 2-positive (HER2+) patients, 696 HER2-negative (HER2-) patients and 49 HER2-unknown patients. Overall, 62.41% of patients received first-line chemotherapy (CT), 21.08% received targeted therapy (TT) and 15.49% received endocrine therapy (ET). For HR+/HER2+ patients, 65.14% received TT, 28.44% received CT, and 5.81% received ET. Compared with patients who received TT, patients who received CT alone, had a significantly worse median PFS (adjusted hazard ratio [HR] =2.59, 95% confidence interval [CI], 1.64-4.10, p<0.001). For HR+/HER2- patients, 77.01% received CT, 20.69% received ET and 1.15% received TT. Compared with patients who received ET, patients who received CT with maintenance therapy had a significantly prolonged median PFS (adjusted HR =0.57, 95% CI, 0.44-0.76, p<0.001). Among HR+/HER2- patients who received CT with maintenance treatment, those with maintenance ET had a longer median PFS than those with maintenance CT, but the difference was not significant (adjusted HR=0.92, 95% CI, 0.64-1.33, p=0.66). Conclusions: This real-world study demonstrates that CT remains the mainstream first-line treatment option for HR+ patients in China. Among patients with HR+/HER2+ ABC, the majority received first-line TT and experienced a PFS benefit. A high percentage of HR+/HER2- patients received CT as first-line therapy in clinical practice. PFS benefit was significantly longer in patients who received CT with maintenance therapy. Moreover, there was no obvious difference in PFS between maintenance ET and CT. Maintenance ET may be a better choice considering its lower toxicity and better quality of life.

20.
J Integr Plant Biol ; 53(1): 35-43, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21205172

RESUMEN

The tau class glutathione S-transferases (GSTs) have important roles in stress tolerance and the detoxification of herbicides in crops and weeds. Structural investigations of a wheat tau GST (TaGSTU4) show two subunit interactions: a hydrogen bond between the Tyr93 and Pro65 from another subunit of the dimer, and two salt bridges between residues Glu78 and side chains of Arg95 and Arg99 in the opposite subunit. By investigating enzyme activities, kinetic parameters and structural characterizations, this study showed the following results: (i) the hydrogen bond interaction between the Tyr93 and Pro65 was not essential for dimerization, but contributed to the enzyme's catalytic activity, thermal stability and affinity towards substrates glutathione and 1-chloro-2, 4-dinitrobenzene; and (ii) two salt bridges mainly contributed to the protein structure stability and catalysis. The results of this study form a structural and functional basis for rational design of more selective and environmentally friendly herbicides.


Asunto(s)
Glutatión Transferasa/metabolismo , Proteínas de Plantas/metabolismo , Triticum/enzimología , Secuencia de Aminoácidos , Secuencia Conservada , Estabilidad de Enzimas , Glutatión Transferasa/genética , Glutatión Transferasa/aislamiento & purificación , Calor , Cinética , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Proteínas de Plantas/genética , Proteínas de Plantas/aislamiento & purificación , Especificidad por Sustrato , Triticum/genética
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